Production of cyclopentane derivatives

ABSTRACT

A process for producing cyclopentane derivatives of the formula   WHEREIN R is hydrogen or a C1 to C6 alkyl group, X is a carboxyl or a carboalkoxy group, and the like; Y and Z each is a hydroxyl group, and the like; and n is an integer of from 5 to 7. The derivatives are useful as medicines. The process of this invention comprises the steps shown in the following reaction scheme:   WHEREIN R, X, Y, Z and n are as defined above, and wherein R&#39;&#39; is lower alkyl group.

United States Patent 1 t [111 3,832,380 Matsui et al. Aug. 27, 1974 PRODUCTION OF CY CLOPENTANE DERIVATIVES [75] Inventors: Masanao Matsui, Tokyo; Junki Katsube, Osaka; Eichi Murayama, Hyogo, all of Japan {73] Assignee: Sumitomo Chemical Co., Ltd.,

' Osaka, Japan [22] Filed: Sept. 9, 1970 [21] Appl. No.: 70,877

Z each is a hydroxyl group, and the like; and n is an integer of from 5 to 7. The derivatives are useful as medicines. The process of this invention comprises the steps shown in the following reaction scheme:

Enol Etherification (01191,); Step 1 (H) O R Catalytic Reduction (CH1) nX Step 2 [30] Foreign Application Priority Data Sept. 9, l969 Japan 44-71785 Nov. 18, 1969 Japan 4492746 Y R M6,, 18, 1969 Japan 44-92747 Cyanamn Jan. 31,1970 Japan 45-8670 FCHIMX I [52] US. Cl. 260/468 D, 260/345.7,260/345.8, 0

260/384, 260/410.9 R, 260/413, 260/448.8 Y R. 260/456, 260/463, 260/464, 260/468 K, Reduction 260/473 R, 260/476 R, 260/488 R, 260/514 Step 4 7 D, 260/5l4 K, 260/570, 260/557 R, 260/559 R 51 Int. Cl. C07C 61/32, C07C 69/74 Y E [58] Field of Search 260/468 D, 514 D, 6 A Q Reduction 2)nX Step 5 [56] References Cited OTHER PUBLlCATlONS Y ON Caton et al.. Tet. Letters, 773 (1972). H (1) Reduction Primary E.raminer-Robert Gerstl Attorney, Agent, or Firm-Sughrue, Rothwell, Mion,

Zinn and Macpeak CH0 K Wittig Reaction [57] ABSTRACT Step A process for producing cyclopentane derivatives of Z the formula 6 Y ll /\R I (CH) X Reduction 2 n 11 01 1 Step 8 Y z R 1)nX H O H Y Y z l R wherein R is hydrogen or a C l to C alkyl group; X is a carboxyl or a carboalkoxy group, and the like; Y and wherein R, X, Y, Z and n are as defined above, and wherein R' is lower alkyl group.

6 Claims, No Drawings PRODUCTION or CYCLOPENTANE DERIVATIVES BAcxoRouNb OF THE INVENTION The present invention relates to a process for the production of cyclopentane derivatives. More particularly. r

the present invention relates to a novel process for pro ducing 3-hydroxyalkenyl-cyclopentane-l, 4-diol derivativeshaving the formula wherein R represents hydrogen or a C, to C alkyl group; wherein X represents a carboxyl group or its homologue, wherein Y and Z each represents a'hydroxyl group or its homologue. and wherein n represents an integer of from 5 to 7.

The cyclopentane derivatives produced by the process of this invention are useful as medicines or intermediates for the production of medicines. These derivatives include the prostaglandins, the prostate hor-' mones and their homologues, and have broad pharmacological activity, for example. as a smooth muscle A few processes for preparing prostaglandins are 7 known. for example, as described in E]. Corey et al., J. Am. Chem. 806.. 90, 3245-3248 (1968), and J.E. Pike et al., J. Am. Chem. 500., 91, 53645378 (1969).

SUMMARY OF THE, INVENTION The present inventors have found a novel process for preparing these compounds, which is completely differ-' ent from these known processes. The process is briefly shown by the following reaction scheme:

(yt-lopontadioiie-euol Ether Derivative (novel material) f. 3 Cyauocyelopex'1tenone Derivative (novel material) (1) Reduction Hydrolysis Step6 3-0yanocyclopeutanoue-l,4-diol Derivative (novel material) 3-Formyleyc1 pentane-l ,4-6101 I Derivative (novel material) I lOl Y Reduction (CHQHX I/ I St Z (VIII) 3-5 0xoalkenyl-cyelopentaim- 1,4-diol Derivative Cyelopentane Derivative in the above reaction sche me,R, XiYjand are as defined above and R representsa lower alkyl group.

The novelty of the process-of this invention includes 7 the steps of producing the novel intermediate products and also the'novel reaction of the cyanation of the enol ether [that; is, the I production of the 3- cyanocyclopentenone derivative (IV) from the cyclopentadione-enol ether derivative (lll)].

An object of the present invention is to provide a process for producing a 3-hydroxyalkenylcyclopentanel ,4-diol derivative which is useful as medicines or'intermediates for the preparation of other medicines.

Another object of this invention is toprovide novel derivatives whichare useful as intermediate products for the production of medicines.

Additional objects and advantages of the present invention :will be apparent fromthe followingidescription.

in the present invention, the tennhomologues of the carboxyl group is a group capable of being readily converted into a carboxyl group or derived from a carboxyl group by a known manner. Examples of such include the C l to C alkoxy-carbonyl group, such as methoxycarbonyl, eth'o xycarbonyl and t-butoxycarbonyl or amido groups such as carbamoyl and methylcarbamoyl groups.

i As described above, in the present invention Y and Z in the aforesaid formula each represents a hydroxyl group or a, homologue of a hydroxyl group. The homologues of a hydroxyl group includes a hydroxyl group protected by a usual protective group. Typical exam- P e n ples of such usual protective groups include etheric protective groups, such as tetrahydropyrariyl ether, tbutyl ether, trimethyl silyl ether, benzyl ether, and trityl ether; acrylic protective groups, such as an acetyl group, a benzoyl group, a benzenesulfonyl group, a toluenesulfonyl group, and a benzyloxycarbonyl group; and a methylidene or a isopropylidene group, when the hydroxyls of Y and Z are in the cis-configuration to each other.

Furthermore, in all of the stages of the present invention, the groups represented by X, Y and'Z can take any desired form within the aforesaid scope or definition depending upon the reaction conditions or the after-treatment. For example, when the protective groups for group Y and group Z are tetrahydropyranyl ether groups, the greater part of these protective .groups is removed under acidic hydrolysis conditions and the groups protected by'such protective groups are converted into hydroxyl. Y

DETAILED DESCRIPTION OF THE INVENTION.

Now, the processof the present invention will be exby reference to the following stages in due order; X

Step l. Production of a Cyclopentatrione-enol Ether Derivative from a Cyclopentatrione Derivative (l):

The reaction of a cyclopentatrione derivative (1) with an alkylating agent gives a cyclopentatrione-enol ether (ll) with a high selectivity with respect to the direction of enol-etherifieation.

Examples of suitable alkylating agents to be used in this stage, stage 1, include a diazoalkane, such as diazomethane; a lower alcohol, such as methanol, ethanol,

and iso-butanol; an alkyl halide, such as methyl iodide, ethyl bromide, and methyl bromide; adialkyl sulfate, such as dimethyl sulfate and diethyl sulfate; and an ortho-formic acid ester. In case diazomethane is used as the alkylating agent, the enol-etherification can be prepared by a conventional manner and the cyclopentatrione derivative (I).

Further, the reaction can also-be carried out,'forexample, by adding an acid such as sulfuric' acid, p-tol uenesulfonic acid, and the like, to a solution ofthe cy- I azeotropic dehydration method. Moreover, wh'erean .alkyl halide or a dialkyl sulfate is used as the'alkylating agent, the reaction is conducted after converting the I cyclopentatrione derivative (1) into the sodium salt,- the potassium salt, and the like, or is conducted in the presence of a metallic compound, such as sodium hydroxide, potassium hydroxide, sodium amide, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium sand, and the like.

Furthermore, where an ortho-formic acid ester is used as the alkylating agent,'the cyclopentatrione derivative (I) is contacted with the ortho-formic acid ester inthe presence of an acidic catalyst, such as sulfuric acid, p-toluenesulfonic acid, boron trifluoride, and the like.

The starting material (I) used in the process of this invention can be obtained by the reaction as shown by the following reaction wherein the reaction formula, 'X 'andn are as defined above and ,R. represents a lower alkyl group. Step2. Production of a Cyclopentadione-eno'l Ether Derivative (Hi) from a Cyclopentatrione-enol Ether Derivative (ll):

The novel cyclopentatrione enol ether derivative (ll) preparedby Stage '1' is subjected in Step 2 to a catalytic reduction to obtain a novel cyclopentadione-enol ether derivative.(l ll).

i The above reaction is achieved by contacting the "compound .(ll) with hydrogen in the presence of a cata- Y lyst whichis conventionallyused in catalyticreduc- .tions. Examples of the catalyst include platinum, palladium, nickel, ruthenium, rhodium, and the like, and,

from the standpoint of easy preparation of the catalyst and the occurrence of less side reactions, the use of palladium as the catalyst is pa'rticularly preferred.

It is preferable to carryout the reaction of this, step in the presence of a solvent which is generally em ployed in catalytic reductions. Suitable solvents are those such as water, methanol, ethanol, propanol, acetic acid. ethyl acetate, benzene and hexane.

The reaction conditions such as hydrogen pressure, reaction temperature and reaction time are conven tional catalytic reduction conditions and they are determin'ed'by .the corelation of them. The progress of the reaction can be detected by the amount of hydrogen absorbed, and the various reaction conditions can "achieved by mixing an ether solution of drazomethane be suitably determined wi thin practical ranges.

'Forexample, when a palladium carbon catalyst is added to the raw material in an arnount'of from several percent to several tens percent, the reaction; proceeds at a satisfactorily practical speed even under atmo- I spheric pressure andat room. temperature.

The novel cyclopentadione-enol 'ether derivative (lll') thus prepared can be purifiedusing, for example, distillation and chromatography, but the reaction product obtained by only filtration and subsequent concentration of the filtrat can be satisfactorily used in the next stage, i

'The novel eyclopentadione-enol ether derivative (lll) thusobtainedshows an ultraviolet absorption at 252mg in ethanol and by analysis of the nuclear mag:

netic resonance spectra; it has bencbr'itirrirdthat the direction of the enolation of the compound (lll).;is as shown by the aforesaid chemical formula.

The cyclopentadione-enol ether derivative (III) also 1,3-dione represented by the formula wherein X and n are as defined above, to an enol etherificationv However, in this case, beside the desired compound (III), the isomer of this compound represented by the formula l OR wherein R, X, and n are as defined above, is a byproduct and it is quite difiicult to separate the byproduct from the desired compound (III) due to the similarity in their properties.

Step 3. Production of a 3-Cyanocyclopentenone Derivative (IV) from the Cyclopentadione-enol Ether Derivative (III):

The cyanation of Step 3 in this invention can be achieved by reacting the cyclopentadione-enol ether derivative (III) with cyanide ion or cyanoaluminum.

It is well known that cyanide ion reacts nucleophillically with a simple ketone or an a, B unsaturated ketone to provide a a-cyanohydrine or a B-cyanoketone, but the cyanation of the cyclopentadione-enol ether derivative of this invention is a novel and unexpected reaction.

The cyanation in the process of this invention can be practiced under various reaction conditions. For example, suitable reaction conditions of using cyanide ion are as follows:

That is, the cyclopentadione-enol ether derivative (III) can be contacted with hydrocyanic acid in an inert solvent in the presence of a basic catalyst, the derivative (Ill) can be contacted with a metal salt of hydrocyanic acid, derivative (Ill) can be contacted with a metal salt of hydrocyanic acid in the presence of a catalyst, derivative (11]) can be contacted with a metal salt of hydrocyanic acid together with an ammonium salt of a strong acid, derivative (Ill) and acetone cyanohydrine can be contacted in the presence of a basic catalyst, and derivative (III) can be contacted with hydrocyanic acid activated by trialkylaluminum.

The reaction modes can be varied depending upon the reaction method employed but they are the same from the standpoint that cyanide ion or activated cyanide ion is caused toreact nucleophillically with the compound (III).

On the other hand, the reaction can be also carried out using an alkylcyanoaluminum. In this case, the reaction modes are as follows:

The compound (III) is caused to react with the alkylcyanoaluminum in the presence or absence of an inert wherein R represents an alkyl group, R" represents an alkoxy group or a halogen, and mis 0 or 1. Typical examples are dimethylalu'minum cyanide, diethylalan alkyluminum cyanide, dipropylaluminum cyanide, diisobutylaluminum cyanide, ethylaluminum chloride cyanide, and the like. These compounds can be prepared by known methods.

The novel 3-cyanocylopentenone derivative (IV) prepared in this step of this invention is a viscous liquid and shows the specific infrared absorption spectra of a nitrile group and an unsaturated ketone group. Also, the material shows a maximum absorption band in the ultraviolet absorption spectra at about 240 mp.

Step 4. Production of a 3-Cyanocylopentanone Derivative (V) from the 3-Cyanopentenone Derivative (IV):

In this step, the 3cyanocyclopentenone derivative (IV) is brought into contact with zinc in the presence of an acidic solvent, whereby the carbon-carbon double bond is selectively reduced and a 3- cyanocyclopentanone derivative (V) is obtained.

Examples of acidic solvents include organic acids, such as acetic acid, formic acid and propionic acid; inorganic acids, such as hydrochloric acid, sulfuric acid, and the like; and the mixtures thereof. In addition, an inert solvent such as an alcohol, benzene, an ether, and hexane can be used, if desired.

The reaction temperature and the reaction period of time can be properly selected but in general it is preferable to conduct the reaction under mild conditions. For example, in the mixed solvent system of acetic acid and hydrochloric acid, the reaction proceeds satisfactorily even under ice-cooling.

Since the 3 -cyanocyclopentanone derivative (V) has three asymmetric carbon atoms, it is theoretically possible that four diastereomers are present. But by the steric selectivity of the reaction, the relative configuration of the substituent at the 2-position and the cyano group at the 3-position appears to be the trans form.

Therefore, the diastereoisomerism of the compound mainly depends on the steric configuration of the hydroxyl or its homologue at the 4-position. These isomers can be separated from each other, if desired, by means of, for example, chromatography. The novel 3- cyanocyclopentanone derivative (V) prepared in step 4 of the process of this invention is generally obtained as an oily material.

The 3-cyanocyclopentanone derivative (V) has no ultraviolet absorption at 240 mp.()\ max EtOH) which is observed in the material (IV) and this phenomenon can be utilized as a method of controlling the reaction.

Step 5. Production of a 3-Cyanocyclopentane-l,4-diol Derivative (IV) from the 3-Cyanocyclopentanone Derivative (V):

- (VI) by reduction with a metal borohydride or a metal tri-t-butoxyaluminum hydride in this stage. Examples of metal borohydrides include various alkali metal borohydrides and alkaline earth metal borohydrides, such as sodium borohydride, potassium borohydride, lithium borohydride, zinc borohydride, magnesium borohydride, calcium borohydride, and the like. st; dium borohydride and potassium borohydride are preferred, because they affect strongly ketone groups but not carboxyl goups or their homologues and cyano groups. Examples of the metal tri-t-butoxyalurninum hydrides include lithium tri-t-butoxyaluminum hydride, sodium tri-t-butoxyaluminum hydride, and the like.

In the reduction of this step it is preferable to employ an inert solvent. Examples of suitable solvents include, in the case of the reduction by a metal borohydride, water; alcohols, such as methanol, ethanol, isopropanol. and the like, and ethers, such as tetrahydrofuran, dioxane, ethyl ether, dimethoxyethane, and the like, and in the case of the reduction by metal tri-tbutoxyaluminum hydride, ethers such as tetrahydrofuran, ethyl ether, dioxane, dimethoxyethane, and the like.

The reducing agents can be used in a stoichiometrically equal or greater amount.

Especially, reducing agents such as sodium borohydride, potassium borohydride, lithium tri-tbutoxyaluminum hydride can be used in a large excess without any detrimental effects because of their reaction selectivity.

Step 6. Production of a 3-Formylcyclopentane-1,4-diol Derivative (VII) from the 3-Cyanocyclopentane-l,4- diol Derivative (VI):

The 3-cyanocyclopentane-1,4-diol derivative (VI) is partially reduced to an aldimine on treatment with stannous chloride and hydrogen chloride or on treatment with lithium aluminum hydride, sodium aluminum hydride or the metal aluminum hydride compound in which from one to three hydrogen atoms thereof have been substituted with lower alkoxy groups and further the aldimine is hydrolyzed into an aldehyde.

The partial reduction of the cyano group with stannous chloride and hydrogen chloride is generally called, including a hydrolysis which will inevitably occur in the subsequent step, the Stephen reaction and various reaction conditions can be employed. That is, in the reaction of this stage, it can be fundamentally achieved by subjecting the 3-cyanocyclopentane-l,4- diol derivative (VI) to contact with stannous chloride and hydrogen chloride in an inert solvent. Examples of the preferred inert solventsinclude ethers, such as diethyl ether, diisopropyl ether, dioxane, and the like. In this reaction, stannous chloride can be used in a great molar excess molar to an amount equal to the amount of the 3-cyanocyclopentane-l ,4-diol derivative (VI) and also hydrogen chloride is usually used in an excess amount. Furthermore, the reaction temperature can be suitably selected in the temperature range lower than the boiling temperature of the solvent to be used.

'Ihe aldimine formed by the reaaction of this step is a complex salt with stannous chloride and hydrochloride, and since the complex salt is in a syrupy or powdered state it can be isolated readily from the reaction system.

When the complex salt-type aldimine thus isolated or the crude reaction product mixture is brought into contact with water, the aldimine is hydrolyzed to provide the desired 3-formylcyclopentane-l ,4-diol derivative (VII), which can be isolated from the reaction system using extraction, and the like.

Preferred examples of the metal aluminum hydride compounds used in the reaction. in the other embodiment of this step of the invention are trialkoxy compounds such as lithium triethoxyaluminum hydride and the like. The reaction by such metal aluminum hydride and the like. On the other hand, the amount of the metal aluminum hydride compound used in the reaction is desirably a stoichiometric amount to the amount of the cyano compound (VI) to be employed or approximately a stoichiometric amount. 7

By ordinary hydrolysis of the aldimine thus obtained, the desired aldehyde compound (VII) can be obtained.

The aldehyde compound (VII) thus obtained can be supplied to the subsequent step as is or can be purified by means of conventional techniques such as chromatography.

Step 7. Production of a 3- y-Oxoalkenylcyclopentane- 1,4-diol Derivative (VIII) from the 3-Formylcyclopentanel ,4-diol Derivative (VII):

The 3-'y-oxoalkenylcyclopentane-I,4-diol derivative (VIII) is obtained by reacting the 3-formylcyclopentane-l,4-diol derivative (VII) with a so-called Wittig reagent represented by the formula R" P=OH-C-R R H (XII) wherein R is as defined above and R represents an alkyl or an aryl group, or a modified Wittig reagent represented by the formula RKDG i x111) wherein R is as defined above and R' represents an aryl group or an alkoxy group.

The reaction can be practiced in various modes, for example, the reaction can be carried out by directly heating the mixture of the starting substances or by heating them in an inert solvent such as diethyl ether, tetrahydrofuran, dioxane, benzene, toluene, xylene, methanol. ethanol, methylene chloride, dimethyl formamide, dialkoxyethane, and the like. The reaction temperature can be suitably selected, and the reaction can proceed even at temperatures lower than room temperature but the reaction rate can be accelerated by heating. Furthermore, the ratio of the amount of the 3-formyleyclopentane-l ,4-diol derivative (VII) to that of the Wittig reagent (XII) or the modified Wittig reagent (XIII) can be appropriately selected. Generally, it is preferable to carry out the reaction in an equimolar ratio or the like.

The desired 3-oxoalkenylcycIopentane-l,4-diol derivative (VIII) can be obtained generally as an oily material and can be isolated and purified using conventional techniques such as chromotagraphy.

compounds is achieved in a conventional manner, that The Wittig reagent or the modified Wittig reagent to be used in the process of this invention can be prepared in a known method. Examples of the Wittig reagent (XII) include forrnylmethylene triphenylphosphorane, acetylmethylene triphenylphosphorane, butanoylmethylene triamylphosphorane, hexanoylmethylene tritolyiphosphorane, hexanoylmethylene tributylphosphorane, and the like.

On the other hand, the modified Wittig reagent: (XIII) is'shown as an anion-type reagent and is prepared by treating a dialkylacylmethyl phosphonate or a diarylacylmethyl phosphine oxide with a base such as phenyl lithium, butyl lithium, or sodium hydride to form the metal salt thereof.

Step 8. Production of a 3-hydroxyalkenylcyclopentane Derivative (IX) from the 3-Oxoalkenylcyclopentane1,4-diol Derivative (VIII):

The 3-oxoalkenylcyclopentane-l,4-diol derivative (VIII) obtained in step 7 is reacted with a metal borohydride or a metal tri-t-butoxyaluminum hydride in an inert solvent in order to obtain the desired 3-hydroxyalkenylcyclopentane derivative (1X). The reaction of this step can be carried out using various reaction conditions within conventional reduction conditions. Examples of metal borohydrides include alkali metal borohydrides, such as sodium borohydride, potassium borohydride, lithium borohydride, and the like, alkaline earth metal borohydrides, such as magnesium borohydride, calcium borohydride, and the like. Use of sodium borohydride and potassium borohydride gives good results because they affect strongly conjugated carbonyls but hardly affect other functional groups of the 3-oxoalkenylcyclopentane-1,4-diol derivative (VIII On the other hand, examples of metal tri-tbutoxyaluminum hydrides include lithium tri-tbutoxyaluminum hydride, sodium tri-tbutoxyaluminum hydride, and the like.

Examples of the inert solvent include, in the case of the reduction using a metal borohydride, water, alcohols such as methanol, ethanol, isopropanol, and the like, and ethers such as diethyl ether. tetrahydrofuran, dioxane, dimethoxyethane, and the like, and in the case of the reduction using a metal tri-t-butoxyaluminum hydride, include ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and the like.

Reaction conditions of temperature and period of I EXAMPLE 1 Production of 1-( 3'-Hydroxy-1 -octenyl)-2-(6- carbomethoxyhexyl)-3,5-dihydroxy-cyclopentane:

(R= n-C,-,Hn; X COOCH Y and Z Ol-l;

Step 1.

Thirty grams (30 g) of 2-(6'-carboxyhexyl) cyclopentan-l,3,4-trione having a melting point of 103C was treated with an ether solution of an excess amount of diazomethane in a conventional manner. The reaction product obtained was subjected to conventional after-treatment and distillation to give 25 g of 2-(6- carbomethoxyhexyl)-3-methoxy-4-oxo-2-cyclopentenl-one, b.p. 165C/0.40.6 mmHg, n 1.4992.

Step 2 An isopropanolic solution (190 ml) of 24 g of 2-( 6 -carbometho xyhexyl) -3-methoxy-4-oxo-2- cyclopenten-l-one prepared in Step 1 and 2.85 g of a 5% palladium carbon catalyst was subjected to catalytic hydrogenation under atmospheric pressure at room temperature until 2.3 liter of hydrogen gas was absorbed. The reaction mixture was treated according to a conventional method to give the desired com pound, 2-(6'-carbomethoxyhexyl)- 3-methoxy-4- hydroxy-2-cyclo-penten- 1 -one.

In the nuclear magnetic resonance spectra of the product, a singlet signal due to the methyl ester proton appeared at 3.65 ppm.

Step 3 a. A toluene solution of diethylaluminum cyanide was prepared by reacting 15.7 g of triethylaluminum with 4.1 g of hydrocyanic acid in 300 ml of toluene. Into the obtained toluene solution of diethylaluminum cyanide was added a mixture of 15.4 g of 2-(6'- carbomethoxy-hexyl )-3-methoxy-4-hydroxy-2- cyclopenten-l-one prepared in Step 2 under cooling and the resultant mixture was allowed to stand for 2 hours at room temperature. The reaction mixture was poured into diluted hydrochloric acid under cooling. The organic layer thus formed was separated, and the aqueous layer was extracted with ether. The combined organic layers were washed with aqueous sodium bicarbonate solution and then water and dried over magnesium sulfate. After evaporation of the solvent, the residual oil was purified using chromatography on silica gel to provide 1 1.6 of 2-(6'-carbomethoxyhexyl)-3- cyano-4-hydroxy-Z-cyclopenten-l-one as an oily material.

b. A mixture of 1.75 g of 2-(6'-carbomethoxyhexyl)- 3-methoxy-4- hydroxy-Z-cyclopenten-l-one, 0.97 g of potassium cyanide, and 0.65 g of ammonium chloride was refluxed for 2.3 hours in a mixture of 1.46 g of water and 14.5 g of tetrahydrofuran with stirring.

After the reaction was over, the liquid portion was separated from the crystalline precipitate by decantation. After the reaction liquid separated was acidified by dropwise addition of hydrochloric acid, the greater part of the tetrahydrofuran was distilled ofi under reduced pressure and the residual oil wa dissolved in ether. The ether layer was washed with water and then aqueous sodium bicarbonate solution and dried over magnesium sulfate. When the ether was distilled off and the oily product thus obtained was pun'fiedby chromatography on silica gel, 0.25 g of 2-(6'- carbomethoxyhexyl )-3-cyano-4-hydroxy-2- cyclopenten-l-one was obtained as an oily substance.

Infrared absorption spectrum (film, unit, cm): 3450, 3225, 1725, 1630, 1440, 1255, 1220 and 1170.

Also, when a nuclear magnetic resonance spectrum (60 Mc) of the above compound were measured, the three protons of the S-membered rings showed specific signals. That is, the proton at the 4-position and the two types of protons at the 5-position show ABX-type signals analyzed approximately first order. 'l'lfeir ehemical shifts and coupling constant (J) were as follows: the proton at the 4-position (5.05, multiplet), the proton at the 5-position at the same side as the proton at the 4- position (2,9, double doub1et,' l 6 cps, 19 cps), and the proton at the 5-position opposite to the proton at the 4position (2.45, double doublet, J 2.5 cps, 19 cps).

All of the nuclear magnetic resonance spectra were obtained using a Varian- 'I'-60, and they were taken in CDCI F 4 Nuclear magnetic resonance spectrumi about 4.8

multiplet. carbinol methine type proton), 3.6(3H, sinwherein H represents,

l l The chemical shifts are given in value, as ppm (8) with respcctto tetram'ethylsilane Step 4 lnto a mixture of 7 g of 2-1b-carbomethoxyhexyl)-3- cyano-4-hydroxy-2-cyclopenten-l-one, 52.5 ml of acetic acid and 55 ml-of 0.5 N hydrochloric acid was added g of zinc powder. After the addition the reaction mixture was stirred for 3 .hoursunder cooling. Thereafter, the zincpowder was removed by filtration, and the filtrate was diluted with water and extracted withether. The ether extract was washed with a diluted Step 6 a. Into a solution of 100 ml of absolute ether and 1.4

g 2-( 6- carbomethoxyhexyl )-3-cyano-l ,4-diacetoxy- -cy'clopentane was introduced a hydrogen chloride gas under ice-cooling until saturated with hydrogen chloride. Further, while continuing the introduction of the hydrogen chloride gas, 1.4 g of anhydrous stannous chloride was'added to the solution 6 times every minutes undericecooling. After further continuing the reaction for 6 hours at room temperature, the reaction aqueous sodium bicarbonate solution and with water and then dried, The solvent was distilledoff'to afford g of ;2( 6'-'carbo meth oxyhexyl 3-cyano-4-hydroxy-cyclopentanone., 1

lnfrared absorption spectrum (cmT): 3450,2250, 1740. I265, 1240, 1205 and ll70. 1

glet methyl ester type protons). a number of hydrogens.

I Step 5 I Intoa suspension of I 8 t g of lithium tri-tbutoxyaluminum hydride in 90ml of absolute tetrahydrofuran was added dropwise 4.0 2; 6!; I

f carbomethoxyhexyl):3 cyano 4-hydroxyv 'cyclopentanone under ice-cooling. The obtained mixture remained'under ice-cooling forl .5 hours and then at room temperature for 0.5 hour. After cooling, acetone'and an aqueous solution saturated with ammonium sulfate were added to the reaction mixture to. de-

g of

compose; the excess lithium tri-t-butoxyaluminum hy-,-. dride and the complex salt'product. The resultant oily layer was extracted with ethyl acetate, and the extract was washed with water, dried and then concentrated to 7 afford 3.2 g of 2-(6-carbomethoxyhexyl-)3-cyano cyclopentane-l,4-diol as an oily substance, whieh was purified using 'chromatogr'aphyon silica gel.

infrared absorption spectrum (uniti emf): 3420 2225. 1730, 1710,1240, 1170. 1085 and 1020.

, T Nuclear magnetic resonance spectrum: about 4.0 (H;

mixture was concentrated under reduced pressure to provide a syrupy material. The material was treated with absoluteether to deposit a yellow powdery material which was recovered by filtration and brought into .,0n1i1 witha cooled aqueous sodium chloride solution by shaking to conduct the" hydrolysis of the product. The ether layer was washed with an aqueous sodium bicarbonate solution and then aqueous sodium chloride solution, and dried over htagnesium sulfate. Ether was distilled off to provide 1 3,5-diacetoxy-cyclopentane' carboaldehyde.

,lnfraredabsorption spectrum (unit; cm"): 2825,

protons).

b. Into a mixturel of 5000f lithium trithox yaluminuin' hydride in. 101.1111"of'absolute'ether was added dropwise'20rnlof a solution (if-.540 mg of 2'-(6'- cyclopentane in absolute-etlierIfAfter-the reaction mixture was stirred'fo'r l 'hour'at'troomtemperature; the 1 1 mixture was treated with25f'ml of 3N-sulfuricj acid under ice-cooling for hydrolysisfwhen'the productwas "extracted with ether and'then treated according toa conventional manner; about 400 mgiof 'a erude product"- 1 oil was obtained. By the analysisofthe iinfrared absorp tion spectra and the nuclear magnetic resonancesped 5' 1 tra, the formation of 2-(6 carbomethoxyhexyl) multiplet, carbinol methinetype, proton at the lposition), about. 4.5 (H; multiplet', carbinol methine methyl ester type protons).

type proton'at thev 4-positio'n). 3.65. (3H, singlet," I

'- s V Y A mixture of 200 ml The cyano-jcyclopentane-diol 1 derivative thus ob tained was contacted with acetieanhydride to yieldthe I corresponding diacetate as an oily substance.

Infrared absorption spectrum (unit: cm)? 2230, 1735, 1360, 1220, ll75 and 1030.

Nuclear magnetic resonance spectrum: about4.9.(H;

' multiplet, methinetypeproton at the l-position), about 5.3 (H, multiplet, methine type proton 8111118 4- 5 position), 3.65 (3H, singlet, methyl ester type protons) and about 2.0 (6H,"s'inglet, acetoxymethyl'type protons).

. Elementary Analysis (71) i N i carboaldehyde' 111 0 450 mgfiof hexanoylmethylene 1 tributylphosphoranewas stirred for 48 hours at room 3.5-diacetoxy-cyclopentane carboaldehyde was i c0 -firmed.

I Step 7 (6 -carb'o-methoxyhexyl )-3 ,5-diacetoxy-cyclopentane temperature. Thereaftenthe reaction mixture was concentrated and the resultant residue was purified using chromatography on silica gel, whereby 350 mg of liquid t pemane was ob i ed. j

' Elementary Analysis 0 v H Calculated (for c mp. 6613.4 8.87 66.34 8.91

Found Infrared absorption spectrum (film, unit, em): 1735, 1695, 1675, 1630, 1370, 1230, 1180 and 1030.

of absolute ether, 47 O mgof 2- blet (J 16 cps) and a double doublet (J 16 cps. .l

= 8 cps). at 6.1 and 6.7, respectively.

Also, the signal of the methyl proton of the acetate appeared as singlets at about 2.0 and the signal of the methine protons at the 3 and the 5 position appeared as a multiplet at about 5.0. Further, the signal of the methyl proton of the methyl ester appeared as a singlet as 3.6 and also the signal of the terminal methyl protons of the octenyl appeared as a triplet (J 7 cps) at 0.9.

Ultraviolet absorption spectrum (A EtOH): 225 m Step 8 Into a mixture of 123 mg of l-(3-oxo-1-octenyl)-2- 6 -carbomethoxyhexyl )-3 .5-diacetoxy-cyclopentane and ml of methanol was added dropwise a mixture of 350 mg of sodium borohydride in ml of methanol under ice-cooling. After the addition, the reaction mixture was stirred for minutes a mixture of 350 mg of sodium borohydride in 35 ml of methanol was added dropwise again, and the stirring was continued for 45 minutes. The reaction mixture was stirred for additional 45 minutes at room temperature. After cooling, acetone was added to decompose the excess of sodium borohydride. The obtained mixture was concentrated under a reduced pressure to yield an oily substance, which was decomposed by the addition of a cold aqueous ammonium chloride solution. The organic layer was extracted with ethyl acetate and treated in a conventional manner to give 100 mg of an oily substance consisting of 1-( 3 -hydroxyl '-octenyl )-2-( 6- carbomethoxyhexyl)-3,5-diacetoxy-cyclopentane and a partly deacetylated compound. The oily substance obtained thus was saponified by reaction with 1 g of a 10 percentaqueous NaOH solution in the presence of 1 g of methanol under cooling. After the saponification, the reaction mixture was acidified, and the separated acidic substance was extracted with ethyl acetate and then treated according to a conventional manner to yield 93 mg of semi-solid of l-(3'-hydroxy-1'- octenyl)-2-(6-carboxyhexy1)-cyclopentane-3.5-diol (Prostagrandin-F Infrared absorption spectrum (unit: cm"): 3775. 3000-2600. 1710. 1265, 1100. 1050 and 970.

Subsequently l-( 3 '-hydroxy- 1 -ocetenyl )-2-( 6'- carboxyhexyl)-cyclopentane-3,5-diol was converted into the corresponding methyl ester on treatment with diazomethane and then purified using chromatography on silica gel to give a semisolid of l-(3'-hydroxy-l'- octenyl)3-(6- carbomethoxyhexyl)-cyclopentane-3,5-diol.

lnfrared absorption spectrum (Cl-1C1 solution, cm): 3450, 1730, 1260, 1090, 1030, and 970.

Nuclear magnetic-resonance spectrum: about 5.6 (2H, multiplet, unsaturated protons at the l-position and the 2'-position), about 4.0 (3H, multiplet, three carbinol type methine protons), 3.7 (3H, singlet, methyl ester type protons), 0.9 (3H, triplet, terminal methyl type protons at the 8-position).

Mass spectrum: 352 (M-l8), 334 (M-36). 280 (M 18-72). M+was not observed because of its weak signal.

' stant, and .1 were as follows:

EXAMPLE 2 Production of l-( 3 -Hydroxy- 1 -octenyl)-2-(6- carboethoxyhexyl )3 .5-diacetoxy-cyclopentane:

Step 1 Five grams (5 g) of 2-(6'-carboethoxyhexyl)-cyclopentanl ,3,4-trione was reacted with diazomethane in ether according to conventional procedures to give 3.8 g of 2-(6-carbethoxyhexyl)-3-methoxy-4-oxo-2- cyclopenten-l-one, b.p. l65170C/0.4-0.6 mmHg.

lnfrared absorption spectrum (film, unit, cm): 1735. 1695, 1620, 1350, 1190, and 1150.

Nuclear magnetic resonance spectrum: 4.28 (3H, singlet, methyl enol ether type protons), 2.88 (2H, singlet. methylene type protons at the 5-position).

Step 2 The procedure similar to that of Step 2 of Example 1 was repeated except that 2.82 g of 2-(6- carbethoxyhexyl )-3-methoxy-4-oxo-2- cyclopenten-l-one and 35 ml of methanol were used 4-oxo-2-cyclopenten-l-one and isopropanol respectively to provide 2.8 g of 2-(6-carboethoxyhexyl)-3 methoxy-4-hydroxy-Z-cyclopenten-l-one as an oily product.

The compound thus prepared had the following properties:

lnfrared absorption spectrum (film, unit, cm): 3400, 1735, 1700 (shoulder), 1625, 1365, 1260, 1170 and 1050.

Nuclear magnetic resonance spectrum (unit: cm"): 4.95 (H. double doublet, J 6 cps and 1.8 cps), 4.13 (3H, singlet 4.12 (2H, quartet, J 7 cps), 2.78 (H, double doublet, .l 18 cps and 6 cps), 2.32 (H, double doublet, .I 18 cps and 1.8 cps) and 1.25 (3H, triplet,

= 7 cps).

A part of the compound thus prepared could be converted into the 4-acetyl compound using conventional methods.

Step 3 a. The procedure similar to that of Step 3 (a) of Example l was repeated using 9.4 g of .2-(6'- carbethoxyhexyl )-3-methoxy-4-hydroxy- 2- cyclopenten-l-one, 8.2 g of triethyl aluminum, 2.0 g of hydrocyanic acid, and a mixed solvent of benzene and toluene to provide 4. 1 g of oily 2-(6'-carbethoxyhexyl)- 3-cyano-4hydroxy-2-cyclopenten-l-one. The properties of the compound thus obtained were as follows:

Infrared absorption spectrum (film, unit, cm):

3450, 2225, 1725, 1630, 1440, 1235 and 1170.

Also, when the nuclear magnetic resonance spectrum of the compound was measured, the three protons of the five-membered ring showed specific signals. That is, the proton at the 4-position and the two protons at the 5-position showed ABX-type analyzed at approximately first order. The chemical shift and coupling con- Proton at the 4'position: 5.05, multiplet; proton at the 5-position at the same side as the proton of the 4- position; 29 double doublet, J 6 cps and 19 cps; and the proton at the -position opposite to the 4-position proton: 2.45 double doublet, J 2.5 cps and 19 cps.

b. According to the procedure similar to that of Step 3 (a) of Example 1, 0.52 g of 2-(6'-carbethoxyhexyl)- 3-methoxy-4-acetoxy-2-cyclopentenl-one prepared in Step 2 was caused to react with diethylaluminum cyanide. Further. the product was purified using chromatography on silica gel to provide 0.25 g of 2-(6- carbethoxyhexyl)-3-cyano-4-acetoxy- 2-cyclopenten- 1 -one as as an oily material. The properties of the product were as follows:

Infrared absorption spectrum (film, cm"): 2239,

1755-1730, 1370, 1240. 1175 and 1045.

Step 4 Into a mixture of 8 ml of acetic acid and 5 ml of 0.1 N hydrochloric acid was dissolved 1.2 g of 2-(6'- carbethoxyhexyl )-3-cyano-4-hyd rox y- 2-cyclopenten-l-one and under ice-cooling the mixture was stirred for 4 hours with the addition of 4 g of zinc powder. The zinc powder in the reaction mixture was filtered off, and after diluting the filtrate with 50 ml of water, the product was extracted with ether and then ethyl acetate. The combined organic layers were washed with aqueous sodium bicarbonate solution and then water and dried.

After evaporation of the solvents, the residue was purified using chromatography on silica gel to provide 050 g of 2-(6-ca rbethoxyhexyl)-3- cyano-4-hydroxy-cyclopentanone. The product thus obtained was an oily material and had the following properties:

Infrared absorption spectrum (film, unit: cm): 3450, 2250, 1740 (broad), 1240 and 1180.

Into an ethanolic solution (38 ml) of 1.26 g of 2-(6 carbethoxy-hexyl )-3-cyano-4-hydroxy-cyclopentanone was added 0.4 g of sodium borohydride under icecooling, followed by stirring for 2 hours with continuing ice-cooling. To the reaction mixture was added ml of acetone to decompose the excess sodium borohydride. Evaporation of the solvent under reduced pressure provided a syrupy residue, which was decomposed by an aqueous ammonium chloride solution.

The resultant organic layer was extracted with ethyl acetate, and the extract was worked up in a usual manner to give 1.06 g of 2-(6'-carbethoxyhexyl)-3-cyanocyclopentane-l ,4-diol.

The properties of the compound thus obtained were as follows:

Infrared absorption spectrum (unit: cm): 3420, 2225, 1730, 1710, 1240, 1170, 1085 and 1020.

Nuclear magnetic resonance spectrum: 4.15 (2H, quartet, ester, methylene protons).

The product was converted into the corresponding tive in a conventional manner.

16 Step 6 a. The procedure similar to that in Step 6 (a) of Example l was repeated using 800 mg of 2-(6'- carbethoxyhexyl)-3-cyano1,4-diacetoxycyclopentane, 800 mg of anhydrous stannous chloride, and 50 ml of absolute ether to provide a crude oily product containing 2-(6'-carbethoxyhexyl)-3,5-

.diacetoxy-cyclopentane carboaldehyde. The product was purified using chromatography. Yield: 275 mg.

b. The procedure similar to that in Step 6(a) of Example was repeated using 350 mg of 2-(6'- carbethoxyhexyl )cyano- 1 ,4-ditetrahydropyranyloxycyclopentane, 250 mg of anhydrous stannous chloride, and 30 ml of absolute ether to provide 250 mg of a crude oily product. By analysis of the infrared absorption spectra and the nuclear magnetic resonance spectra, it was confirmed that the product contained the desired carboaldehyde derivative. Also, by subjecting a part of the product to thin-layer chromatography, the desired 2-( 6 -carboethoxyhexyl )-3 ,5 -dihydroxycyclopentane carboaldehyde was detected by a spot showing a low R; value.

Step 7 A mixture of 250 mg of 2-(6'-carboethoxyhexyl)-3,5- diacetoxy-cyclopentane carboaldehyde and 200 mg of sodium salt-type diethyl-hexanolymethyl phosphonate in dimethoxy ethane was stirred for 48 hours at room temperature. the reaction liquid was poured into cold diluted hydrochloric acid. The resultant oily produce was extracted with ether and the ethereal extract was post-treated in a conventional manner to provide 200 mg of oily l-( 3 -oxo-l '-octenyl)2-(6- carbethoxyhyexyl )-3 ,5-diacetoxycyclopentane.

The nuclear magnetic resonance spectrum of the compound was almost same as those of the carbomethoxy compound obtained in Step 7 of Example 1 except that the methylene proton signal of the ethyl ester appeared as a quartet (J 7 cps) at 4.1.

Step 8 Into a suspension of 1.0 g of lithium tri-tbutoxyaluminum hydride in 8 m1 of absolute tetrahydrofuran was added dropwise 200 mg of 1-(3'-oxo-1'- ocetenyl)-2 (6-carboethoxyhexyl)-3,5-diacetoxycyclopentane under ice-cooling. The resultant mixture was stirred for 1.5 hours under ice-cooling and then for 1 hour at room temperature. After cooling, acetone and an aqueous solution saturated with ammonium sulfate were added to the reaction mixture to decompose the excess lithium tri-t-butoxyaluminum hydride and the complex salt product.

The resultant oily layer was extracted with ethyl acetate, and the extract was washed with water, dried and then concentrated to afford mg of 1-(3-hydroxy- 1 '-octeny1)-2-( 6-carbethoxyhexy1)-3,5-diacetoxycyclopentane. The properties of this compound were as follows:

In its nuclear magnetic resonance spectrum, the signal due to the olefinic protons appeared at about 5.6 as a multiplet. The signal due to the methine protons at the 3- and the 5-position appeared at about 5.0 as a multiplet. Moreover, specific signals at about 2.0 (singlet, acetoxy methyl protons) and 4.15 (quartet, ester methylene protons) were observed.

EXAMPLE 3 Production of l-( 3'-Hydroxyl '-propcnyl)-2-(6- carbethoxyhexyl)-3,5-diacetoxy-cyclopentanc (R H; X COOC H,,; Y Z OCOCH;;; n

Steps 1-6 According to the procedures similar to those in Steps 1-6 of Example 2, 2-(6'-carbethoxyhexyl)-3,5- diacetoxy-cyclopentane carboaldehyde was obtained.

Step 7 Step 8 In the nuclear magnetic resonance spectrum of the compound, the aldehyde proton appeared as a doublet (J 8 cps) at about 9.5.

Into an ethanolic solution (10 ml) of 80 mg of l-(3'- oxol propenyl)-2-(6-carbethoxyhexyl)-3,5-diacetoxycyclopentane was added 200 mg of sodium borohydride under ice-cooling, followed by stirring for an additional hour with continuing ice-cooling.

The mixture obtained was worked up by a usual manner to give an oily material containing the objective l-( 3'-hydroxyl -propenyl)-2- 6'-carbethoxyhexyl )-3 ,5-diacetoxy-cyclopentane.

In its nuclear magnetic resonance spectrum, the signal due to the olefinic protons of the propenyl chain was observed at about 5.5 as a multiplet.

What is claimed is:

1. A process for preparing cyclopentanes of the for-' mula:

wherein R is a member selected from the group consisting of H and an alkyl group of from one to six carbon atoms; wherein X is a member selected from the group consisting of a carboxyl group and a COOR"" group. wherein R"" is an alkyl group ranging from one to six carbon atoms; wherein Y and Z each is a member selected from the group consisting of a hydroxyl group and a hydroxyl group protected by a protective group selected from the group consisting of a tetrahydro- 18 l. reacting a cyclopentatrione derivative having the formula 0 o I ll (cHmx wherein X and n are as defined above, with an alkylat 1 ing agent to obtain a cyclopentatrione-enol ether derivative having the formula wherein X and n are as defined above and R is a lower alkyl group;

2. contacting the cyclopentatrione-enol ether derivativeprepared in Step 1 with hydrogen in the presence of a catalyst to provide a cyclopentadioneenol ether derivative having the formula i g (oHanx i 0 wherein R, X, Y, and n are as defined above;

3. reacting the cyclopentadione-enol ether derivative prepared in Step 2 with a member selected from the group consisting of cyanide ion and an alkylcyanoaluminum compound to obtain a 3- cyanocyclopentenone derivative having the formula Y CN wherein X, Y and n are as defined above;

4. contacting the 3-cyanocyclopentenone derivative prepared in Step 3 with zinc in the presence of an acidic solvent to obtain a 3-cyano-cyclopentanone derivative represented by the formula Y C'N cu=)..x

wherein X, Y and n are as defined abovei i reducing the 3-cyanocyclopentanone derivative prepared in Step 4 to provide a 3-cyanocyclopeniiune-l,4-diol derivative having the formula Y CN wherein X, Y, Z and n are as defined above;

(CH2) BX wherein R is as defined above and R" is a member selected from the group consisting of an alkyl group and an aryl group, and a modified Wittig reagent having the formula R (XIII) wherein R is as defined above and R' is selected from the group consisting of an aryl group and an alkoxy group, to provide a 3-oxoalkenylcyclopentane-l ,4-diol derivative having the formula vun wherein R, X, Z and n are as defined above; and

8. reducing the 3-oxoalkenylcyclopentane-l,4-diol derivative prepared in Step 7 to provide the cyclopentane derivative and separating the obtained cyclopentane compound from the reaction mixture; and

said cyclopentane compound of the formula set forth above, wherein R"" represents the hydrogen atom being prepared by first preparing a cyclopentane compound of the formula described above wherein R"" represents a member selected from the group consisting of an ethyl group and a methyl group, in

Y accordance with steps (I) (8) of this claim and subsequently, hydrolyzing the thus obtained ethyl or methyl cyclopentane derivative to produce the hydro form, and

separating the thus obtained hydro form of said eyclopentane compound from the reaction mixture,

said process for preparing said cyclopentane compounds wherein R represents a member selected from the group consisting of a hydrogen atom and an alkyl group of from one to six carbon atoms being carried out at room temperature and standard pressure.

2. The process according to claim 1, wherein the objective cyclopentane is selected from the group consisting of 2-(6-carboxyhexyl)-3-(3'-hydroxy-1'-octenyl)- cyclopentane-1,4-diol, the methyl ester thereof and the ethyl ester thereof.

3. The process according to claim 2, wherein said alkylating agent in Step 1 is selected from the group consisting of a diazoalkane, an alcohol, an alkyl halide, a dialkyl sulfate, and an alkyl ortho-formic acid ester.

4. The process according to claim 2, wherein said alkylcyano aluminum in Step 3 is selected from the group consisting of dimethylaluminum cyanide, diethylaluminum cyanide, dipropylaluminum cyanide, di-isopropylaluminum cyanide, and an ethyl aluminum chloride cyanide.

5. The process according to claim 2, wherein said acidic solvent in Step 4 is selected from the group consisting of formic acid, acetic acid, propionic acid, hydrochloric acid and sulfuric acid.

6. The process according to claim 1, wherein R is an n-pentyl group and n is 6. 

2. contacting the cyclopentatrione-enol ether derivative prepared in Step 1 with hydrogen in the presence of a catalyst to provide a cyclopentadione-enol ether derivative having the formula
 2. The process according to claim 1, wherein the objective cyclopentane is selected from the group consisting of 2-(6''-carboxyhexyl)-3-(3''-hydroxy-1''-octenyl)-cyclopentane-1,4-diol, the methyl ester thereof and the ethyl ester thereof.
 3. The process according to claim 2, wherein said alkylating agent in Step 1 is selected from the group consisting of a diazoalkane, an alcohol, an alkyl halide, a dialkyl sulfate, and an alkyl ortho-formic acid ester.
 3. reacting the cyclopentadione-enol ether derivative prepared in Step 2 with a member selected from the group consisting of cyanide ion and an alkylcyanoaluminum compound to obtain a 3-cyanocyclopentenone derivative having the formula
 4. contacting the 3-cyanocyclopentenone derivative prepared in Step 3 with zinc in the presence of an acidic solvent to obtain a 3-cyano-cyclopentanone derivative represented by the formula
 4. The process according to claim 2, wherein said alkylcyano aluminum in Step 3 is selected from the group consisting of dimethylaluminum cyanide, diethylaluminum cyanide, dipropylaluminum cyanide, di-isopropylaluminum cyanide, and an ethyl aluminum chloride cyanide.
 5. The process according to claim 2, wherein said acidic solvent in Step 4 is selected from the group consisting of formic acid, acetic acid, propionic acid, hydrochloric acid and sulfuric acid.
 5. reducing the 3-cyanocyclopentanone derivative prepared in Step 4 to provide a 3-cyanocyclopentane-1,4-diol derivative having the formula
 6. The process according to claim 1, wherein R is an n-pentyl group and n is
 6. 6. contacting the 3-cyanocyclopentane-1,4-diol derivative prepared in Step 5 with a member selected from the group consisting of stannous chlorode and hydrogen chloride and lithium aluminum hydride, sodium aluminum hydride and a metal aluminum hydride compound, and a metal aluminum hydride compound wherein from one to three of the hydrogen atoms are replaced with a lower alkoxy group to obtain an aldimine compound and hydrolyzing the resultant aldimine compound thus obtained to provide a 3-formylcyclopentane-1,4-diol derivative having the formula
 7. reacting the 3-formlcyclopentane-1,4-diol derivative prepared in Step 6 with a member selected from the group consisting of a Wittig reagent having the formula
 8. reducing the 3-oxoalkenylcyclopentane-1,4-diol derivative prepared in Step 7 to provide the cyclopentane derivative and separating the obtained cyclopentane compound from the reaction mixture; and said cyclopentane compound of the formula set forth above, wherein R'''''''' represents the hydrogen atom being prepared by first preparing a cyclopentane compound of the formula described above wherein R'''''''' represents a member selected from the group consisting of an ethyl group and a methyl group, in accordance with steps (1) - (8) of this claim and subsequently, hydrolyzing the thus obtained ethyl or methyl cyclopentane derivative to produce the hydro form, and separating the thus obtained hydro form of said cyclopentane compound from the reaction mixture, said process for preparing said cyclopentane compounds wherein R represents a member selected from the group consisting of a hydrogen atom and an alkyl group of from one to six carbon atoms being carried out at room temperature and standard pressure. 